Magazine
JULY 2010
Volume 30 No. 07
Direct
route
Drop-in bio-based
alternatives
Fuel circle
Biorefineries of
the future
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Sustainability
Getting to the point: Direct bio-b
Dennis McGrew of Genomatica outlines the case for directly produced, drop-in bio-based
replacements for traditional manufacturing methods
I
n the last 18 months, the chemicals industry
has made significant strides toward more biobased production. One year ago, a survey conducted by Genomatica and ICIS showed that 57%
of industry executives said their companies should
reduce their exposure to the petroleum-based
commodity market. Companies also acknowledged that their customers have expressed real
interest in chemicals based on renewable materials.
More than half of the executives in the survey,
however, said that cost was the most prohibitive
part of a sustainable chemicals programme.
Consumer attitudes, volatile petroleum markets
and global demand contraction have converged
for a unique moment of interest and demand for
sustainable chemicals, but cost continues to be the
key barrier to adoption.
If capacity rebounds in the next three to five
years, as some analysts predict, it will present an
interesting opportunity to introduce new process
technologies that use renewable feedstocks to
manufacture chemicals. These new processes can
drive the start of a transformation of the chemicals
industry.
However, helping the industry to transition
from petroleum-based feedstocks to renewable
feedstocks will not happen overnight. As shown in
the survey, common wisdom holds that transitioning to a more sustainable industry will raise costs
and further squeeze tight margins.
Making the industry more environmentally sustainable at the cost of economic viability is not an
option. Genomatica believes strongly that sustainability must come at a lower cost and that innovative biotechnology can deliver sustainable solutions at lower costs, especially when direct production routes eliminate as many intermediate
processing steps as possible and the resulting
materials are equivalent to conventional ones used
today, enabling them to be dropped into existing
downstream value chains.
Metabolic engineering platform
To fulfill this daunting goal of low-cost sustainability, our research teams have explored hundreds of
routes to dozens of products. Genomatica’s core
technologies for metabolic engineering, combined
with our laboratory and process engineering capabilities, have enabled us to explore a broad portfolio of processes to generate a range of chemical
intermediates.
Early assessment and IP around platform molecules like succinic acid and 3HP were de-emphasised in favour of more direct production routes to
existing, large chemical intermediates like 1,4butanediol (BDO). Our other ongoing efforts also
include various acrylates, polyamide (PA, or nylon)
intermediates, solvents and surfactants. Published
patent applications demonstrate the breadth of
routes available, with development priority given
to those with the best opportunity to deliver
breakthrough cost reductions of >25% over the
best available conventional technology in large,
growing chemical intermediate markets.
Challenges with indirect routes
In August 2004, the US Department of Energy
(DOE) published a study intended to evaluate and
compare more than 300 molecules from the point
of view of technological feasibility, size of potential
market and interest to the chemicals industry. It
identified priorities for the top 12 chemicals of
greatest interest.
These 12 are often called platform molecules,
because they may serve as a platform for producing a variety of derivatives. However, they generally provide an indirect route to the chemical inter-
mediates that are large consumers of fossil fuels
today. Such routes face several potential challenges that may ultimately affect economics.
Unwanted by-products are often generated that
impact not only costs, but also the process’s environmental footprint, while additional processing
steps typically require more unit operations with
the inherent added capital, energy and operating
expense, as well as creating the potential for yield
losses.
Finally, the chemical intermediates purportedly
derived from these platform molecules often have
substantially larger markets than the platform
chemicals themselves, requiring large infrastructure investments to reach sufficient economies of
scale to make a significant impact on fossil fuel
use.
Unintended consequences
A concern, especially for larger-scale chemical
intermediate production, is the potential for undesirable co-products from indirect production
routes. Organic acids, some considered as potential platform molecules, are an example of this.
Lactic acid can be produced from bio-based
feedstocks through fermentation but requires
direct acidification, esterification and hydrolysis
through reactive distillation to purify and provide
a useful chemical intermediate. Direct acidification
produces large quantities of gypsum co-product,
which may not be pure enough for industrial use.
As processes scale up, even a relatively minor
waste stream can become problematic, adding
disposal costs and reducing yield. Improvements
in technology may substantially reduce undesirable co-products, but will likely not eliminate them
entirely.
Platform chemical routes like organic acids may
be effective for some small speciality chemicals or
Alcohol
Water
Lime
Sugars
Fermentation
Sulphuric
acid
Direct
Acidification
Hydrolysis
Ester
Lactic
acid
Esterification
Water
Gypsum
Figure 1 - Traditional route to lactic acid
32
July 2010 Speciality Chemicals Magazine
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Sustainability
based chemical production
Sugar
Fermentation
Acidification
Separations
Hydrogenation
a
Separations
Sugar
Fermentation
Separations
BDO
BDO
b
Figure 2 - Succinic acid (a) & direct (b) routes to BDO
niche ‘green’ markets, but for larger volume
chemical intermediates like 1,4-BDO, acrylates or
nylon intermediates, the waste products could
become problematic.
Lactic acid also shows the challenge of multiple
unit operations required to isolate and purify it as
a raw material for subsequent chemical conversion to the targeted chemical intermediates
(Figure 1). Further, impurities associated with its
production can be problematic for downstream
products, affecting yields and separations, especially as one strives for lower costs. These challenges may also manifest themselves for other
organic acids developed as platform chemicals.
Keeping it simple
Whilst platform molecules may indeed provide
bio-based routes to various chemical intermediates, the additional necessary steps run counter to
the goal of a low-cost solution. To foster widespread adoption of sustainable chemicals, the new
processes must cost less than traditional methods.
We see our direct production route to 1,4-BDO
(Figure 2) as a prime example, eliminating the
need for the isolation and purification of succinic
acid and the subsequent high-temperature and
high-pressure steps for BDO conversion via catalytic hydrogenation. We estimate that the additional processing steps between succinic acid and
butanediol could add at least 20 cts/lb (€0.36/kg)
to the cost of the final product.
In both academic journals and media outlets,
there is concern that succinic acid production has
not yet reached economic competitiveness with
1,2 Most sources
traditional production methods.
say the cost of separating and purifying it from the
fermentation broth is the largest barrier to economic production for most applications.
For the large global PA market, we have filed a
patent application for bio-based direct route to
several intermediates, potentially opening up fully
bio-based PA 6 and PA 6,6. We typically file
patents on a range of routes, but pursue only the
most direct ones, those that can be achieved in a
single organism and the simplest possible process.
We achieve this through metabolic engineering
and genetic modification.
By contrast, many of the other approaches for
pursuing bio-based nylon routes are indirect production routes through platform chemicals including lysine, a common bio-based amino acid. For
instance, researchers at Michigan State University
have patented a process for converting L-lysine
from natural materials to -caprolactam, a precursor to PA 6, in a handful of processing steps with
a yield of about 75%. The -caprolactam is then
polymerised into PA 6, which has a huge global
market.
Genomatica’s proposed routes have significantly fewer steps and those steps are simpler, especially in the separations of intermediates and
desired end-products (Figure 3).
Industrial inertia dictates that a simpler replacement technology will spread faster through the
industry where the simplicity leads to lower costs.
Building replacement processes with the minimum number of unit operations for current largemarket chemical intermediates is vital. Instead of
requiring additional processing steps and additional capital investments, more direct production
route will ease adoption when compared to indirect methods.
Leveraging infrastructure
The effective and rapid transformation of the
chemicals industry toward greater production of
bio-based materials will require leveraging existing infrastructure to the greatest extent possible.
Historically, substitutes for existing chemical intermediates or polymers have required substantial
changes in existing infrastructure or downstream
derivative production.
These changes can create barriers to market
adoption, extending time for speed-to-scale of
new products and offsetting economies gained
with bio-based production. Success critically relies
on performance advantages due to these barriers.
We feel that an approach with chemically identical, performance-equivalent chemicals and polymers at lower cost than conventional processes
Speciality Chemicals Magazine July 2010
will be required to drive the large-scale transformation of the chemicals industry. Instead of developing new markets for chemicals or requiring new
infrastructure or supply chains, direct production
of existing chemical intermediates can quickly
drop into current markets and leverage substantial
downstream infrastructure that is already in place
globally.
At present, succinic acid serves a relatively small
world market of about 40,000 tonnes/year.
Proponents contend that the market could grow
100-fold if the bio-based variety is made at a lower
price than the petrochemical method. Whilst the
global market for lysine is substantially larger than
succinic acid at more than 700,000 tonnes/year, it
remains far smaller than the 4,000,000
tonnes/year market for caprolactam.
It is difficult to believe that economical production of large-scale chemical intermediates can be
driven through these indirect routes, as a significant amount of capital will need to be invested for
the platform molecule, in addition to capital for
conversion to target chemical intermediates.
Chemicals producers are making important
strides to serve this sustainable market demand
and allow the industry to diversify away from
petrochemical feedstocks. Several processes are
nearing commercialisation, as small demonstration
facilities start up and industry leaders, including
BASF and DSM, have announced the commercialisation of bio-based succinic acid in the coming
years.
However, most industry efforts appear focused
on lower volume specialities, green niches, like
deicing fluids, and potentially new polymers, like
polybutylene succinate, rather than as a platform
molecule for the production of BDO. While these
efforts establish more important examples of successful bio-based processes, we believe the path
to open large chemical intermediate markets is
through drop-in, low-cost alternatives via the most
direct production method possible.
The International Sugar Organisation’s (ISO)
first industrial bio-products market study, ‘Market
Potential of Sugarcane & Beet Bio-products’,
33
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Sustainability
Sugar
Fermentation
to lysine
Lysine-HCI
separations
Acidification
Ion exchange
Evaporation
Neutralisation
Crystallisation
Lysine cyclisation
& separations
Alkalinisation
Salt, solvent &
water removal
Deamination
& -Caprolactam
recovery
Addition of KOH
& NH2OSO3H
Amine removal
Sublimation
Polymerisation
Sugar
Fermentation
to 6-ACA
6-ACA
separations
pH adjustment
Evaporation
Crystallisation
Polymerisation
PA6
a
PA6
b
Figure 3 - Lysine-based (a) & direct 6-ACA-based (b) routes to PA 6
charts new territory in sugar cane and sugar beet
market analysis by focusing on the emerging
opportunity for sugar-derived chemicals, polymers
and bioplastics. Genomatica’s sugar-based process
for producing 1,4-BDO is presented in the
‘Biobased Chemicals’ section titled as a promising
technology.3
Aside from bio-polyethylene, which the ISO
identifies as a key bioplastics opportunity, the
report finds that of all chemicals studied BDO has
“the best potential in the near term”, in part due
to the direct nature of its production in the
Genomatica process and consequent lower production costs.
BDO’s large market size, it adds, combined
with Genomatica’s process, gives bio-based BDO
several advantages over bio-based succinic acid,
which has a significantly smaller market and
requires additional conversion to create chemicals
such as BDO, with yield losses and cost increases
in the process.
Direct to 1,4-BDO
If a process is to produce the target chemicals
directly, a microorganism must be engineered to
produce the chemical and serve as an effective
biocatalyst. Driving the titre, productivity and yield
of the process are some of the most important
metrics to produce an economically viable, sustainable chemical, and organism performance is
critical to success.
If the fermentation process can produce more
quickly, that lowers the overall cost of production.
Genomatica uses genetic engineering and adaptive evolution to improve the rate of production
from fermentation processes.
Our research teams have focused on increasing
titres as we move toward commercialisation. This
spring, they achieved an important milestone with
our flagship butanediol process, achieving over 80
gm/litre titres in 30 litre fermentations.
Simultaneously, we are reducing by-products and
seeing improved yields.
Unlike many organisms that make a targeted
chemical as a by-product of their own growth, our
technology platform allows us to link the organism’s growth to the production of the target chemical. We genetically knock out the pathways to the
other by-products, so the organism must produce
our target chemical to survive. All of these
advances are important and our economic models
estimate that our process is now at least cost-competitive with traditional methods of manufacturing.
We continue to refine the process and we are
confident that we can achieve a significant cost
advantage through an even higher titre and
improved yield. In less than two and a half years,
we moved from the first detectable quantities of
BDO ever shown in a fermentation to over 80
gm/litre from raw sugar (sucrose). This threshold
matches the cost of current petroleum-based
BDO production, and we are well on our way to
the next threshold, which will give us a strong cost
advantage.
We find that traditional chemicals producers are
becoming more knowledgeable and comfortable
about titre and other key metrics of bio-based
chemical production. They understand the keys to
viable production and recognise both our
progress and the power of our integrated development process.
Next steps
Looking to the future, a few more key milestones
will mark the industry’s progress toward a more
sustainable future. We have scaled our flagship
BDO process up 100-fold, as part of the preparation for a demonstration plant in 2011, and have
recently shown equivalent fermentation performance at both 30 and 3,000 litre scales.
Our initial engagements with existing BDO
consumers and producers indicate that our biobased BDO is promising from both analytical and
application standpoints. Pilot-scale production and
the demonstration plant will allow for further
large-scale sampling and downstream conversion
34
testing to demonstrate effective use in key derivative products, including PBT, PTMEG and TPU.
We have also demonstrated the utility of our
organism and process across a variety of commercial feedstocks, with no apparent loss in key fermentation performance metrics or final product
quality. As with our BDO process, the growth of
the industry will depend on continued conversion
of bio-based products to end products, compatibility with existing derivative infrastructure and
cost-effective manufacturing.
A wide range of companies are innovating to
make the chemicals industry more sustainable and
to allow for the use of other feedstocks. Many different bio-based applications will find a range of
niche markets, but a truly widespread revolution
will require lower costs and simple conversion.
Direct, cost-effective production has greater
potential to revolutionise the chemicals industry,
expanding sustainability more quickly and bringing increased profitability at the same time.
For more information, please contact:
Dennis McGrew
Genomatica, Inc.
10520 Wateridge Circle
San Diego
CA 92121
USA
Tel: +1 858 362 8578
E-mail: [email protected]
Website: www.genomatica.com
References:
1. J.B. McKinlay, C. Vieille & J.G. Zeikus, Prospects
for a Bio-Based Succinate Industry, Applied
Microbiology & Biotechnology 2006 , 76, 727-740
2. A. Cukalovic & C.V. Stevens, Feasibility of
Production Methods for Succinic Acid Derivatives: A
Marriage of Renewable Resources & Chemical
Technology, Biofuels, Bioproducts & Biorefining
August 2008 , 6, 505-529
3. www.isosugar.org/PDF%20files/MECAS(09)17;%
20MECAS(09)18;%20MECAS(09)19.pdf
July 2010 Speciality Chemicals Magazine
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